rs973978463

Variant names:

• chr12-52609252-C-G
• rs973978463
• NM_175068.3:c.1361G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-52609252-C-G
• chr12-52609252-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_175068.3(KRT73):​c.1361G>C​(p.Ser454Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S454N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KRT73 NM_175068.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.80
• Publications: 0 publications found

Genes affected

KRT73 (HGNC:28928): (keratin 73) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This gene encodes a protein that is expressed in the inner root sheath of hair follicles. The type II keratins are clustered in a region of chromosome 12q13.[provided by RefSeq, Jun 2009]

KRT73-AS1 (HGNC:49607): (KRT73 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36661056).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175068.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT73	NM_175068.3	MANE Select	c.1361G>C	p.Ser454Thr	missense	Exon 8 of 9	NP_778238.1	Q86Y46-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT73	ENST00000305748.7	TSL:1 MANE Select	c.1361G>C	p.Ser454Thr	missense	Exon 8 of 9	ENSP00000307014.3	Q86Y46-1
	KRT73	ENST00000552855.1	TSL:3	c.596G>C	p.Ser199Thr	missense	Exon 5 of 6	ENSP00000449081.1	H0YIC5
	KRT73	ENST00000546934.1	TSL:2	n.1754G>C		non_coding_transcript_exon	Exon 7 of 8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251480 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461350 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727052

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111556

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.37	T
MetaSVM	Uncertain	0.43	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.8
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.47
Sift	Uncertain	0.022	D
Sift4G	Benign	0.23	T
Polyphen		0.97	D
Vest4		0.42
MutPred		0.37		Gain of catalytic residue at S456 (P = 0)
MVP		0.44
MPC		0.53
ClinPred		0.94	D
GERP RS		4.8
Varity_R		0.24
gMVP		0.27
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs973978463; hg19: chr12-53003036;